5f6k

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Crystal structure of the MLL3-Ash2L-RbBP5 complex

Structural highlights

5f6k is a 7 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.411Å
Ligands:SAH, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ASH2L_HUMAN Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. May function as a transcriptional regulator. May play a role in hematopoiesis.[1] [2]

Publication Abstract from PubMed

The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the transcriptional regulation of genes involved in haematopoiesis and development. The methyltransferase activity of MLL1, by itself severely compromised, is stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are shared by all MLL family complexes. However, the molecular mechanism of how these factors regulate the activity of MLL proteins still remains poorly understood. Here we show that a minimized human RBBP5-ASH2L heterodimer is the structural unit that interacts with and activates all MLL family histone methyltransferases. Our structural, biochemical and computational analyses reveal a two-step activation mechanism of MLL family proteins. These findings provide unprecedented insights into the common theme and functional plasticity in complex assembly and activity regulation of MLL family methyltransferases, and also suggest a universal regulation mechanism for most histone methyltransferases.

Structural basis for activity regulation of MLL family methyltransferases.,Li Y, Han J, Zhang Y, Cao F, Liu Z, Li S, Wu J, Hu C, Wang Y, Shuai J, Chen J, Cao L, Li D, Shi P, Tian C, Zhang J, Dou Y, Li G, Chen Y, Lei M Nature. 2016 Feb 25;530(7591):447-52. doi: 10.1038/nature16952. Epub 2016 Feb 17. PMID:26886794[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
33 reviews cite this structure
Writing, erasing and reading histone lysine methylations.
Hyun et al. (2017)
32 more
71 other articles
No citations found

See Also

References

  1. ↑ Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes Dev. 2003 Apr 1;17(7):896-911. PMID:12670868 doi:10.1101/gad.252103
  2. ↑ Patel A, Dharmarajan V, Vought VE, Cosgrove MS. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. J Biol Chem. 2009 Sep 4;284(36):24242-56. Epub 2009 Jun 25. PMID:19556245 doi:M109.014498
  3. ↑ Li Y, Han J, Zhang Y, Cao F, Liu Z, Li S, Wu J, Hu C, Wang Y, Shuai J, Chen J, Cao L, Li D, Shi P, Tian C, Zhang J, Dou Y, Li G, Chen Y, Lei M. Structural basis for activity regulation of MLL family methyltransferases. Nature. 2016 Feb 25;530(7591):447-52. doi: 10.1038/nature16952. Epub 2016 Feb 17. PMID:26886794 doi:http://dx.doi.org/10.1038/nature16952

Contents


PDB ID 5f6k

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